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Concentration-effect relationships of NSAID.

¹Department of Medicine, University of Washington, Seattle 98195.

The Journal of Rheumatology. Supplement

|October 1, 1988

Summary

Plasma drug levels of nonsteroidal anti-inflammatory drugs (NSAID) often fail to predict treatment success. This may be due to poor study design or because tissue concentrations, not plasma levels, are key to NSAID efficacy.

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Area of Science:

Pharmacology
Biomedical Science
Drug Discovery

Background:

Plasma concentrations of nonsteroidal anti-inflammatory drugs (NSAID) generally show poor correlation with therapeutic outcomes.
This discrepancy may stem from experimental design flaws or the indirect relationship between plasma and target tissue drug levels.

Purpose of the Study:

To investigate the relationship between NSAID concentrations in synovial effusions and therapeutic response.
To explore factors influencing NSAID levels within inflamed tissues.

Main Methods:

Review of factors affecting NSAID distribution and action in target tissues.
Consideration of elimination kinetics, protein binding, lipophilicity, and tissue perfusion.
Analysis of NSAID concentrations in synovial fluid.

Main Results:

Plasma NSAID concentrations may not accurately reflect drug levels at the site of action.
Factors like tissue blood flow and cellular uptake significantly influence local drug concentrations.

Conclusions:

Synovial fluid NSAID concentrations are likely more relevant to therapeutic efficacy than plasma levels.
Further research should focus on tissue-level pharmacokinetics to optimize NSAID therapy.

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